Synthesis of linezolid metabolites PNU-142300 and PNU-142586 toward the exploration of metabolite-related events

Research output: Contribution to journalArticle

Abstract

Linezolid (1) is an oxazolidinone antibiotic that is partially metabolized in vivo via ring cleavage of its morpholine moiety to mainly form two metabolites, PNU-142300 (2) and PNU-142586 (3). It is supposed that accumulation of 2 and 3 in patients with renal insufficiency may cause thrombocytopenia, one of the adverse effects of linezolid. However, the poor availability of 2 and 3 has hindered further investigation of the clinical significance of the accumulation of these metabolites. In this paper, we synthesized metabolites 2 and 3 via a common synthetic intermediate, 4; this will encourage further exploration of events related to these metabolites and lead to improved clinical use of linezolid.

Original languageEnglish
Pages (from-to)194-199
Number of pages6
JournalChemical and Pharmaceutical Bulletin
Volume65
Issue number2
DOIs
Publication statusPublished - 2017

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Linezolid
Metabolites
Oxazolidinones
Thrombocytopenia
Renal Insufficiency
Anti-Bacterial Agents
Availability

Keywords

  • Linezolid
  • Metabolite
  • Oxazolidinone
  • Tetrabutylammonium salt
  • Thrombocytopenia

ASJC Scopus subject areas

  • Chemistry(all)
  • Drug Discovery

Cite this

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title = "Synthesis of linezolid metabolites PNU-142300 and PNU-142586 toward the exploration of metabolite-related events",
abstract = "Linezolid (1) is an oxazolidinone antibiotic that is partially metabolized in vivo via ring cleavage of its morpholine moiety to mainly form two metabolites, PNU-142300 (2) and PNU-142586 (3). It is supposed that accumulation of 2 and 3 in patients with renal insufficiency may cause thrombocytopenia, one of the adverse effects of linezolid. However, the poor availability of 2 and 3 has hindered further investigation of the clinical significance of the accumulation of these metabolites. In this paper, we synthesized metabolites 2 and 3 via a common synthetic intermediate, 4; this will encourage further exploration of events related to these metabolites and lead to improved clinical use of linezolid.",
keywords = "Linezolid, Metabolite, Oxazolidinone, Tetrabutylammonium salt, Thrombocytopenia",
author = "Kengo Hanaya and Kazuaki Matsumoto and Yuta Yokoyama and Junko Kizu and Mitsuru Shoji and Takeshi Sugai",
year = "2017",
doi = "10.1248/cpb.c16-00831",
language = "English",
volume = "65",
pages = "194--199",
journal = "Chemical and Pharmaceutical Bulletin",
issn = "0009-2363",
publisher = "Pharmaceutical Society of Japan",
number = "2",

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TY - JOUR

T1 - Synthesis of linezolid metabolites PNU-142300 and PNU-142586 toward the exploration of metabolite-related events

AU - Hanaya, Kengo

AU - Matsumoto, Kazuaki

AU - Yokoyama, Yuta

AU - Kizu, Junko

AU - Shoji, Mitsuru

AU - Sugai, Takeshi

PY - 2017

Y1 - 2017

N2 - Linezolid (1) is an oxazolidinone antibiotic that is partially metabolized in vivo via ring cleavage of its morpholine moiety to mainly form two metabolites, PNU-142300 (2) and PNU-142586 (3). It is supposed that accumulation of 2 and 3 in patients with renal insufficiency may cause thrombocytopenia, one of the adverse effects of linezolid. However, the poor availability of 2 and 3 has hindered further investigation of the clinical significance of the accumulation of these metabolites. In this paper, we synthesized metabolites 2 and 3 via a common synthetic intermediate, 4; this will encourage further exploration of events related to these metabolites and lead to improved clinical use of linezolid.

AB - Linezolid (1) is an oxazolidinone antibiotic that is partially metabolized in vivo via ring cleavage of its morpholine moiety to mainly form two metabolites, PNU-142300 (2) and PNU-142586 (3). It is supposed that accumulation of 2 and 3 in patients with renal insufficiency may cause thrombocytopenia, one of the adverse effects of linezolid. However, the poor availability of 2 and 3 has hindered further investigation of the clinical significance of the accumulation of these metabolites. In this paper, we synthesized metabolites 2 and 3 via a common synthetic intermediate, 4; this will encourage further exploration of events related to these metabolites and lead to improved clinical use of linezolid.

KW - Linezolid

KW - Metabolite

KW - Oxazolidinone

KW - Tetrabutylammonium salt

KW - Thrombocytopenia

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